Effect of calvatic acid and its analogs on ornithine decarboxylase activity in tumour cells.
Calvatic acid (p-carboxyphenylazoxycyanide) is an antibiotic containing an azoxycyano group that displays carcinostatic activity. In the present work it has been shown that in AH-130 hepatoma and K562 leukemia cells the antibiotic, at low concentration, decreases ornithine decarboxylase (ODC) levels. The change depends on two summative effects of the drug, impairment of overall protein synthesis and inhibition of enzyme activity. Some analogs of calvatic acid have been tested in order to gain more insight into the structure-activity relationship. The decarboxylated derivative phenylazoxycyanide proved to be more effective in reducing protein synthesis and ODC activity in the whole tumor cells. The rapidly growing K562 cells displayed high sensitivity to this compound. Calvatic acid analogs devoid of the cyano group were less effective on the same parameters.
Brossa
O
O
Department of Clinic and Biological Sciences, University of Turin, Italy.
Gadoni
E
E
Olivero
A
A
Seccia
M
M
Miglietta
A
A
Gabriel
L
L
Gravela
E
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D001565:Benzoates; D009570:Nitriles; D065108:Ornithine Decarboxylase Inhibitors; C010057:calvatic acid